MicroRNA-21 Regulates Metabolic Adaptation of Pathogenic TH17 cells and Controls Autoimmune Inflammation

TH17 cells exhibit great heterogeneity and variable functional states in vivo. However, the precise molecular mechanism for this heterogeneity is poorly understood. Here we demonstrate that homeostatic and pathogenic TH17 cells in vivo show discrete chromatin states at conserved regulatory region of TH17 cell-related transcription factors, metabolic regulators and microRNAs. We find the regulatory region of miR-21 shows great more chromatin accessibility in CNS infiltrating pathogenic TH17 cells compared to ileum homeostatic TH17 cells. We further demonstrate that homeostatic and pathogenic TH17 cells have distinct metabolic states, and miR-21 is essential for the highly glycolytic state of pathogenic TH17 cells. MiR-21-deficient TH17 cells show less glycolytic activity and express less pathogenic TH17 cell signature genes. These findings suggest that miR-21 is a critical regulator for the metabolic adaptation of pathogenic TH17 cells under autoimmune inflammation.